Variants of unknown significance on chromosomal microarray analysis: parental perspectives

Abstract

Chromosomal microarray is the recommended first-tier genetic test when a child presents with idiopathic developmental delay (DD), intellectual disability (ID), and/ or autism spectrum disorder (ASD). Microarray may discover variants of unknown clinical significance (VUS) and been suggested to cause parental stress and anxiety. A retrospective, mixed methods study investigated parental perceptions of chromosomal microarray results that contain VUS. Surveys were sent to parents of children with DD/ID/ASD following a VUS result to seek information regarding parental understanding of the result, perceived value, and perceptions of child vulnerability and parental stress. Parents reported that chromosomal microarray was important for understanding their child's diagnosis and they were satisfied with the information. A majority of parents reported high confidence in their ability to explain a VUS result to others. Of the parents who reported they received support, many reported that the support was from a genetic counselor. Based on these results, VUS results are important to parents of children with DD/ID/ ASD and genetic counseling regarding VUS results contributes positively to both parental understanding and support.

Parents’ Perspectives on Variants of Uncertain Significance from Chromosome Microarray Analysis

“…Others discussed that the test results empowered them to seek out medical, educational, therapeutic, and financial services. Similar benefits of receiving results were also noted in previous studies (Jez et al 2015;Reiff et al 2012;Whitmarsh et al 2007). This suggests that even in the face of ambiguity, endorsing a parental perspective of active engagement with healthcare providers, teachers, and others, as well as accessing resources, can help to facilitate adaptation and coping.…”

“…Parents' intentions to comply with recommended follow-up were also investigated, and we noted strong motivation to do so, but with some misunderstanding of key components of this process. Our findings support those of previous studies which indicated incomplete comprehension and struggles with personal interpretation of results (Jez et al 2015;Reiff et al 2012), and further contribute to the literature surrounding patient understanding, interpretation and adaptation to genetic results of uncertain significance.…”

“…Others expressed that their perceptions were instinctive or even based on hope, perhaps reflecting a strong desire for answers. A recent study reported that many parents viewed a VUS as having provided an explanation and therefore had experienced relief (Jez et al 2015), a sentiment echoed by some participants in this study. Of course, the harm in this personal interpretation would be the possibility that families may not pursue additional follow-up evaluation, potentially preventing the establishment of a definitive diagnosis and/or the necessity for readaptation should an alternative diagnosis be made.…”

“…When examining preferences for results from microarrays, Turbitt et al (2014) found respondents favored knowing about variants for their potential practical benefits, though they also agreed that such results would raise parental anxiety (Turbitt et al 2014). A recent study assessed parental understanding, perceived value, perceptions of child vulnerability, and parental stress after receiving a VUS (Jez et al 2015). While findings were consistent with ongoing difficulties with ambiguity, perceptions that the VUS had provided some explanation and relief were also noted.…”

Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders

“…This process will allow us as a community to realize the maximum benefit of the increased detection rate achieved through array and interpretation optimization. Furthermore, VOUS results have been clearly demonstrated to be of great importance to parents of patients with DD/ID/ASD [34,40,41,42,43]. …”